Two-dimensional gel electrophoresis was used to compare the changes in mouse epidermal
proteins induced by the potent
tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), by the moderate promoter mechanical abrasion, and by the weakly promoting hyperplasiogenic agents
mezerein and
ethylphenylpropiolate. Evidence is presented which indicates that TPA caused many changes in the epidermal
protein profiles especially related to the
keratins which are the major differentiation product of the epidermis. The
keratin modification progresses with time after TPA treatment, resulting in a
keratin pattern which resembles that of newborn mouse epidermis. The criteria used for the identification of the
keratins were extractability, isoelectric points, molecular weights, filament formation in vitro, immunological cross-reactivity,
amino acid composition, and
peptide mapping. Several other
protein changes were evident in the more soluble epidermal
proteins which were also prominent in the newborn epidermis. These
protein alterations are observed not only early during the TPA induction of
hyperplasia and
inflammation at 48 and 72 hr but also in 1- and 2-week samples in which the morphology of the epidermis has returned to normal.
Mezerein and abrasion produced
protein changes similar to those induced by TPA.
Ethylphenylpropiolate-induced
protein modifications not only occurred at later times compared with either
mezerein or TPA but also were less in magnitude. However, although many of the
protein modifications induced by TPA appear to be associated with the hyperplasiogenic properties of TPA, the major difference between a potent promoter like TPA and a weak promoter like
ethylphenylpropiolate appeared to be related to the magnitude of the response and the time of appearance of the
protein changes.